It has recently become apparent that the production of lipid peroxidation in the living body and the radical reaction accompanying the production of lipid peroxidation exert various adverse influences on the living body via membrane damage and cell damage. Therefore, it has been made various attempts of applying antioxidants and lipid peroxidation production inhibitors to drugs, and various kinds of studies on antioxidants have been made. As the antioxidants, for example, pharmaceutical compositions containing a specific quinone derivative used for treatment and prophylaxis of endotoxin shock ascribable to inflammation or infection; hydroxamic acid derivatives having a cell proliferation inhibitory action and a neovascularization inhibitory action used for treatment and prophylaxis of autoimmune diseases; and 2,3-dihydrobenzofuran derivatives which are useful as antioxidizing agents and radical scavengers (for example, Patent Document 1) are known. Also, imidazole-based compounds having an anti-hyperlipidemia action, which are useful for treatment and prophylaxis of arteriosclerosis (for example, Patent Document 2); and benzothiazinecarboxamide which has an anti-arthritis activity and is represented by the following formula (for example, Patent Document 3) are known.

Furthermore, there are carbonylaminophenylimidazole derivatives (refer to Patent Document 4); aminodihydrobenzofuran derivatives having a lipid peroxidation production inhibitory action which is useful as a preventive or therapeutic agent for various diseases such as arteriosclerosis, hepatopathy and cerebrovascular disorder (Patent Document 5); antihyperlipidemic agents containing a phenylazole compound (Patent Document 6); dihydrobenzofuran derivatives which significantly ameliorate damage on lipid, protein, carbohydrate and DNA caused as a result of oxidative stress which arises when an antioxidative defense system is insufficient (Patent Document 7); and optically active aminodihydrobenzofuran derivatives which are useful for amelioration, treatment and prophylaxis of brain functional disorder accompanying rebral apoplexy and head injury (Patent Document 8).
Regardless of large energy need, since supply of energy depends on blood circulation, brain is drastically weak against ischemia. When cerebral blood flow stops by various reasons, resulting in cerebral ischemia, active oxygen species are generated due to mitochondria disorder and an increase in calcium content in nerve cells. Also it is known that oxygen radicals are explosively generated on reopening of blood stream after ischemia. It is considered that these active oxygen species finally exerts an action on lipid, protein and nucleic acid and oxidize them, thereby causing cell death. Antioxidants are used for treatment of these disease states, and edaravone is permitted as a brain protective agent and used in Japan.
As lipoxygenase (LO) which causes the addition of oxygen to an unsaturated fatty acid typified by arachidonic acid, for example, 5-LO, 8-LO, 12-LO and 15-LO are known according to the site to which oxygen is added. Among these, 5-LO is a primary enzyme which synthesizes leukotriene as a strong inflammation mediator. Lukotrienes is involved in various inflammatory diseases such as asthma, rheumatic arthritis, inflammatory colitis and psoriasis and control thereof is useful for treatment of these diseases. It is known that 12-LO and 15-LO react with linoleic acid, cholesterol ester, phospholipids and low density lipoprotein (LDL), in addition to arachidonic acid, and causes the addition of oxygen to the unsaturated fatty acid. It is known that macrophage infinitely incorporate oxidation-modified LDL via a scavenger receptor to form foam cells, which is a first step of formation of arteriosclerotic focus It is also apparent that 12-LO and 15-LO are expressed in a high level in the macrophage and is essential as a trigger of oxidative modification of LDL. Control of them is useful for treatment of various diseases caused by arteriosclerosis.
When arachidonic acid as a precursor of fatty acid is separated from phospholipids of a cellular membrane, it is converted into 20-HETE by a 20-hydroxyeicosatetraenoic acid (HETE) synthase. It is known that 20-HETE contracts or extends microvasculature or causes cell proliferation in main organs such as kidney and brain blood vessel. It is suggested that it is involved in an important physiological effect in the living body and has a close relation with disease states of kidney diseases, cerebrovascular diseases and circulatory diseases. Furthermore, it is reported that a phenylazole derivative has an inhibitory action of the 20-HETE synthase.
It is considered that, regarding most ophthalmic diseases which are frequently caused by aging such as cataract or macular degeneration, oxidative stress involved in free radicals and active oxygen is one of onset factors. It is known that the retina is a tissue which is likely to be influenced by aging, together with crystalline lens. The retina is likely to be influenced by various free radicals because it contains a large amount of a higher unsaturated fatty acid and a nutrient is supplied from both retinal vessel and choriocapillaries, and also consumes a large amount of oxygen. For example, light such as sunlight supplied throughout one's life is a typical one of oxidative stress to the retina. Visible light and infrared light account for almost all of sunlight which arrives at the ground, and several percents of ultraviolet light contained therein strongly interacts with the living body as compared with visible light and infrared light and thus it drastically exerts an adverse influence on health. Ultraviolet light is classified into UV-A (320 to 400 nm), UV-B (280 to 320 nm) and UV-C (190 to 280 nm) according to a difference in wavelength, and the action and intensity to the living body vary. It has been considered that ultraviolet light having a wavelength of 290 nm or less having particularly strong cytotoxicity is absorbed by the ozone layer of stratosphere and hardly arrives at the ground. However, it is considered that the appearance of ozone hole, which is considered to be caused by environmental disruption, recently increases the dose of ultraviolet light which arrives at the earth and also dermatopathy and cutaneous cancer involved in ultraviolet light increase in the south hemisphere, and thus retinopathy may significantly increase by the influence of UV-A which arrives at the retina.
Age-related macular degeneration among ophthalmic diseases is retinopathy which may frequently cause ablepsia, and it is considered that ten million people develop slight symptoms and 450,000 or more are suffering from visual deficit caused by this disease in the States. Also in Japan in which the aging society has already been established rapidly, there is a fear of an increase in this disease. A mechanism of the onset of macular degeneration is unclear. However, it is considered that progression of this lesion is involved in the peroxidation reaction due to light absorption at the retina. Also it is considered that the appearance of a lipofuscin-like fluorescent material referred to as drusen is recognized at the prophase of the onset and also lipofuscin is produced by bonding an aldehyde as a secondary decomposition product of lipid peroxidation with a protein, and thus the lipid peroxidation reaction due to ultraviolet light or visible light at the retina can induce this retinopathy.
A therapeutic agent for retinal diseases containing a specific dihydrofuran derivative, which is useful for prophylaxis and treatment of retinal diseases due to an antioxidation action, and an agent for change in visual acuity and retina, including macular degeneration of the retina, which contains propionyl L-carnitine or pharmaceutically acceptable salts thereof and carotenoid, are known.    Patent Document 1: Japanese Unexamined Patent Application, First Publication No. Hei 2-121975    Patent Document 2: Pamphlet of International Publication No. 95/29163    Patent Document 3: Specification of German Patent Publication DE 3,407,505    Patent Document 4: Japanese Unexamined Patent Application, First Publication No. Sho 55-69567    Patent Document 5: Japanese Unexamined Patent Application, First Publication No. Hei 5-140142    Patent Document 6: Pamphlet of International Publication No. WO00/006550    Patent Document 7: Pamphlet of International Publication No. WO96/28437    Patent Document 8: Japanese Unexamined Patent Application, First Publication No. Hei 6-228136